Improvement of the efficacy and persistence of academic CAR-T cells for the treatment of mature-B cell malignancies
Speaker: Dr. Beatriz Martín-Antonio - Department of Experimental Hematology - Fundación Jimenez Diaz (Madrid)
Host: Manuel Serrano, PhD
Organizer: IRB Barcelona
Date: Friday 12 March 2021, 12.00h
In the recent years, adoptive cell immunotherapy administering chimeric antigen receptor (CAR)-modified T cells has established as a new method of treatment for patients with relapsed or refractory hematological malignancies. Despite complete and permanent responses achieved in some malignancies, such as pediatric B-lymphoblastic leukemias, other diseases such as multiple myeloma, do not achieve permanent responses mainly due to lack of persistence of CAR-T cells. Furthermore, additional mechanisms of relapse include loss of expression of the target antigen, which presents different incidence depending on the disease treated and the target antigen. To improve these obstacles, a high variety of novel CAR constructs with additional functions are being developed. Nevertheless, whereas many of them have shown success in pre-clinical models, clinical results have not been successful. In this regard, CAR-T cells are already well-equipped to eliminate tumor cells; however, during immune-tumor cell communication relevant events occur that might be responsible for this lack of efficacy of CAR-T cells and the development of resistance mechanisms of the tumor cell. Importantly, lessons learned from the immune system could give us clues to enhance the efficacy of this treatment. Here, I will present the stages that we went through to develop academic CAR-T cells directed against BCMA which are currently being administered in multiple myeloma patients in a Clinical trial (EudraCT code: 2019-001472-11). Moreover, the impact that different cytokines might have in the activity of CAR-T cells will be presented. Last, a much lower efficacy of CAR-NK cells vs CAR-T cells will be revealed and, on the other side, how NK cells can be used to enhance the efficacy of CAR-T cells.